Caspase-3 (Cysteine-aspartic acid protease 3) (CASP3)

Caspase-3 is a critical executioner enzyme in the apoptotic (programmed cell death) pathway, belonging to the cysteine-aspartic acid protease family [UniProt P42574; Porter & Jänicke, 1999]. It exists as an inactive 32 kDa zymogen (procaspase-3) that is activated through proteolytic cleavage by initiator caspases, such as Caspase-8 or Caspase-9, in response to internal or external death signals [Elmore, 2007]. Once activated, Caspase-3 cleaves a wide array of cellular substrates, including poly(ADP-ribose) polymerase (PARP), leading to DNA fragmentation and the systematic dismantling of the cell [Porter & Jänicke, 1999; PubChem]. In many cancers, Caspase-3 activation is suppressed by endogenous inhibitors like XIAP (X-linked Inhibitor of Apoptosis Protein), allowing for uncontrolled cell proliferation and survival [Fulda & Vucic, 2012]. Therapeutic strategies focusing on the indirect activation of Caspase-3 involve the use of small molecules like SMAC mimetics or Bcl-2 inhibitors to overcome these inhibitors or restore pro-apoptotic signaling [Fulda & Vucic, 2012; Westphal et al., 2014]. These approaches aim to selectively induce apoptosis in malignant cells while sparing healthy tissue, though managing systemic toxicity and potential off-target effects remains a significant clinical challenge [Fulda & Vucic, 2012].

Other names

Cysteine-aspartic acid protease 3CPP32SCA-1ApopainYamaProcaspase-3CASP-3

Indirect activation of Caspase-3 is achieved by modulating upstream apoptotic regulators, such as inhibiting Inhibitor of Apoptosis Proteins (IAPs) like XIAP or antagonizing anti-apoptotic Bcl-2 family members [Fulda & Vucic, 2012; Westphal et al., 2014]. These actions facilitate the conversion of the inactive zymogen procaspase-3 into its active heterotetrameric form, which then executes the final stages of programmed cell death by cleaving essential cellular substrates [UniProt P42574; Elmore, 2007].